Four human gene therapy clinical protocols, as well as one human gene transfer protocol, are now underway in the Clinical Center. The gene transfer protocol involves the insertion of a marker gene (the NeoR gene carried in the retroviral vector LNL6) into tumor infiltrating lymphocytes (TIL). The purpose is to better understand TIL adoptive immunotherapy in the treatment of advanced cancer, specifically malignant melanoma. The first human gene therapy protocol was begun September, 1990. The goal is treatment of adenosine deaminase (ADA) deficiency (a cause of Severe Combined Immunodeficiency, a fatal disease of children) by inserting a normal ADA gene into the lymphocytes of patients. The other gene therapy protocols are for the treatment of advanced cancer and involve inserting cytokine genes into TIL cells or autologous tumor cells followed by giving the gene-modified cells back to the patient.